A cure for some patients with HIV, which has become a sort scientific Holy Grail, seemed like it might have been within reach back in 2013 when researchers reported that they’d banished the virus in a Mississippi child through aggressive treatment immediately after birth.
The report gave scientists hope that high doses of antiretroviral drugs given to newborns or newly infected adults might be able to eradicate the virus permanently.
But those hopes were dashed when federal health officials announced at the end of last week that the child is once again showing signs of the virus.
“[The news] is sad and it tells us we have to use the term cure very carefully,” said Dr. Hans-Peter Kiem, a stem cell transplant researcher in the Fred Hutchinson Cancer Research Center's Clinical Research Division. “For many cancer treatments it takes years before we use the word cure. We also have to be mindful that this virus has an unusually unique way of hiding in patients and thus requires very careful study designs.”
The search for a cure for HIV and the disease it causes, AIDS, is relatively new. For a long time scientists felt that at best they might be able to hold the disease at bay, allowing people to live relatively normal lives while taking a cocktail of drugs.
But over the last decade, researchers have been looking into the possibility of finding an actual cure. The initial reports on the Mississippi child sparked so much enthusiasm researchers had begun to organize a worldwide trial that would include nearly 500 babies whose mothers were HIV infected, but who had not been tested or treated before giving birth.
That trial has now been put on hold. But it’s far from the only avenue of research.
At Fred Hutch, Kiem and colleague Dr. Keith Jerome, an expert in viral infections at the Hutch’s Vaccine and Infectious Diseases Division, have been investigating the possibility of curing HIV with genetically modified stem cells. They lead a group called defeatHIV and in August will be co-hosting the Hutch's second Conference on Cell and Gene Therapy for HIV Cure.
Their research was sparked by the experiences of Seattle born Timothy Ray Brown, 48, who is one of the few HIV infected people who may have beat the disease.
Brown, who was designated in early reports as the “Berlin patient” was living in Germany in 1995 when he was diagnosed with HIV. He later developed acute myeloid leukemia and in 2007 his doctor recommended a stem cell transplant, a procedure that had been pioneered at Fred Hutch.
Being an ambitious fellow, the doctor thought he might try to cure not just Brown’s cancer, but also his HIV, by finding a stem cell donor who carried two copies of an exceedingly rare gene mutation that confers a natural resistance to the virus.
Brown’s leukemia returned after the first treatment, but after a second, his cancer seemed cured – apparently along with his HIV.
Kiem and Jerome don’t plan to give HIV patients stem cell transplants. Instead they are working on techniques to modify an HIV-infected patient’s own stem cells to knock out or disable the gene that acts as a doorway to the virus.
The Hutch-led collaboration is one of three distinct approaches funded by the NIH and called the Martin Delaney collaboratories, after an early HIV/AIDS educator and activist. The University of North Carolina, Chapel Hill, is leading a team working on an approach called “shock and kill” or “kick and kill” that is looking for drugs that can wake the virus from its latency stage so that antiretroviral drugs can kill the hidden reservoirs. A group based at the University of California, San Francisco is focused on the role of the immune system and the inflammatory reaction to establishing and maintaining the reservoir.
According to Jerome and Kiem, a successful cure will likely borrow from all three. Drugs used to wake up the viruses could facilitate gene therapy approaches by making them work more efficiently, they said. Inflammation plays a big part not only in HIV persistence but in engraftment of genetically engineered cells.
“We collaborate among the collaboratories,” Jerome said in an earlier interview. “The ultimate cure is very likely to be a combination of approaches.”
Fred Hutch is hosting Cell & Gene Therapy for HIV Cure 2014, which will be held Aug. 26-27. The conference is intended to foster scientific relationships and collaboration among national and international scientific researchers, early investigators, post docs and graduate students. Scholarships and travel grants are available. For more information, click here.